Effects of formulation on the bioavailability of lutein and zeaxanthin: a randomized, double-blind, cross-over, comparative, single-dose study in healthy subjects.

PURPOSE: Lutein and zeaxanthin are macular pigments with a protective function in the retina. These xanthophylls must be obtained from the diet or added to foods or supplements via easy-to-use, stable formulations. The technique employed to produce these formulations may affect the bioavailability of the xanthophylls. METHODS: Forty-eight healthy volunteers were randomized into this double-blind, cross-over study investigating the plasma kinetics of lutein provided as two different beadlet formulations. Subjects (n = 48) received a single dose of 20 mg of lutein as either a starch-matrix ("SMB", FloraGLO® Lutein 5 %) or as a cross-linked alginate-matrix beadlet ("AMB", Lyc-O-Lutein 20 %) formulation. Plasma concentrations of lutein and zeaxanthin were measured at 0, 1, 3, 6, 9, 12, 14, 24, 26, 28, 32, 36, 48, 72, 168, and 672 h. RESULTS: The mean plasma AUC(0-72h), AUC(0-672h), and C(max) for total lutein and zeaxanthin and their all-E-isomers were significantly increased (p < 0.001) from pre-dose concentrations in response to SMB and AMB. There was no difference in lutein T max between the two test articles. However, by 14 h post-dose, total plasma lutein increased by 7 % with AMB and by 126 % with SMB. Total lutein AUC(0-72h) and AUC(0-672h) were 1.8-fold and 1.3-fold higher, respectively, for SMB compared to AMB. Both formulations were well tolerated by subjects in this study. CONCLUSION: These findings confirm that the bioavailability of lutein and zeaxanthin critically depends on the formulation used and document a superiority of the starch-based over the alginate-based product in this study.

Apolipoprotein E genotype is associated with macular pigment optical density.

PURPOSE: Age-related macular degeneration (AMD) is the most common cause of blindness in older people in developed countries, and risk factors for this condition may be classified as genetic and environmental. Apolipoprotein E is putatively involved in the transport of the macular pigment (MP) carotenoids lutein (L) and zeaxanthin (Z) in serum and may also influence retinal capture of these compounds. This study was designed to investigate the relationship between macular pigment optical density (MPOD) and ApoE genotype. METHODS: This was a cross-sectional study of 302 healthy adult subjects. Dietary intake of L and Z was assessed by food frequency questionnaire, and MPOD was measured by customized heterochromatic flicker photometry. Serum L and Z were measured by HPLC. ApoE genotyping was performed by direct polymerase chain reaction amplification and DNA nucleotide sequencing from peripheral blood. RESULTS: Genotype data were available on 300 of the 302 (99.3%) subjects. The mean (+/- SD) age of the subjects in this study was 47.89 +/- 11.05 (range, 21-66) years. Subjects were classed into one of three ApoE genotype groups, as follows: group 1, epsilon2epsilon2 or epsilon2epsilon3; group 2, epsilon3epsilon3; group 3, epsilon2epsilon4 or epsilon3epsilon4 or epsilon4epsilon4. All three groups were statistically comparable in terms of age, sex, body mass index, cigarette smoking, and dietary and serum levels of L and Z. There was a statistically significant association between ApoE genotype and MPOD. Subjects who had at least one epsilon4 allele had a higher MPOD across the macula than subjects without this allele (group 1 MPOD area, 0.70 +/- 0.40; group 2 MPOD area, 0.67 +/- 0.42; group 3 MPOD area, 0.85 +/- 0.46; one-way ANOVA, P = 0.014. CONCLUSIONS: These results suggest that ApoE genotype status is associated with MPOD. This association may explain, at least in part, the putative protective effect of the epsilon4 allele for AMD and is consistent with the view that apolipoprotein profile influences the transport and/or retinal capture of circulating L and/or Z.

Rhodopsin-induced experimental autoimmune uveoretinitis: dose-dependent clinicopathological features.

We have studied the clinicopathological features of experimental autoimmune uveoretinitis (EAU) induced in Lewis rats by injection of different doses of rhodopsin and its illuminated form opsin. Rhodopsin consistently appears to be more pathogenic than opsin. Injected in Freund's complete adjuvant and pertussis adjuvant 50 micrograms of rhodopsin induces a frequency of severe EAU similar to 250 micrograms of opsin. Intensity, frequency and location of ocular inflammation are markedly dose dependent. At high dose (100-250 micrograms), rhodopsin induces severe bilateral uveoretinitis in all animals, which starts with acute inflammation of the anterior eye segment at day 10-12 followed by chorioretinitis (predominantly retinitis) which results in complete elimination of the photoreceptor cells. At low dose (20 micrograms), rhodopsin induces mild transient inflammation in 60% of the animals, mainly consisting of mild posterior retinitis which starts at day 20 and leads to a typical multiple focal destruction of the photoreceptor cells. Intermediate doses cause an intermediate type of disease. Omission of pertussis adjuvant lowers the frequency of severe disease at low doses of rhodopsin, delays its onset and changes its features. The last characteristic has been observed in particular at intermediate doses (50-100 micrograms). In these cases, EAU usually starts by cell infiltration of the vitreous, while the anterior segment is only mildly affected. Without pertussis adjuvant the pathogenicity of opsin is low. Even in both adjuvants severe EAU can only be evoked by a high dose of opsin. Although there exists a marked difference in uveitogenicity between rhodopsin and opsin, the immunogenicity is similar and seems not to be correlated with their pathogenicity.

Experimental retinal autoimmunity (ERA) in strain 13 guinea pigs: induction of ERA-retinopathy with rhodopsin.

Strain 13 guinea pigs injected with either homologous or bovine rhodopsin, the visual pigment of the retinal outer segments, in complete Freund's adjuvant (CFA) developed experimental retinal autoimmunity (ERA). Initial clinical signs of disease were seen within 21 days after immunization. Pathologic examination of the eyes revealed the presence of inflammatory cells in the choroid and the destruction of the retinal rod outer segments. The unique feature of this disease is that despite the destruction of the inner and outer segments of the retina, at no time is there a substantial inflammatory cell infiltrate. Even as late as 45 days after immunization, when destruction of the retinal ganglion cell layer was noted, no inflammatory cells were detected in the retina. These findings suggest that the retinal inner and outer segments are the target of the autoimmune reaction subsequent to sensitization with purified rhodopsin-CFA.